1. Field of the Invention
The present invention relates to a method and apparatus for estimating the degree of neuronal impairment in the brain cortex, which can be used for early estimation of a senile dementia disorder.
2. Description of the Related Art
With respect to senile dementia, it is statistically said that about 30% of nonagenarians are in dementia. This senile dementia is becoming a serious problem for the coming aging society.
Accordingly, such a dementia disorder should be preferably found as early as possible and treated before it results in a serious state. The judgment of the dementia disorder has been conventionally performed by various manual methods as follows:
(1) Hasegawa""s Dementia Rating Scale (HDS)
The HDS method is devised for screening demented old people from normal aged ones. The HDS is composed of questions which the normal old or aged people without an intellectual disorder can relatively easily answer. This method can be normally performed in 5-10 minutes.
The questions include 11 items such as xe2x80x9cmemory and registrationxe2x80x9d, which are main items, xe2x80x9corientationxe2x80x9d, xe2x80x9ccalculationxe2x80x9d, and xe2x80x9cgeneral common sensexe2x80x9d. Predetermined weighting are performed to the points, based on the rate of passing the question items, according to the difficulty.
Also, with revised evaluation items, the HDS is replaced with the Hasegawa""s Dementia rating Scale Revised (HDS-R) in which the examination can be performed if the birthday of the person himself/herself is solely confirmed.
(2) National Mental Research Dementia Screening Test
This national mental research dementia screening test is a standardized simplified test for accurately screening old people suspected of being dementia from healthy old people.
Namely, it is a screening test which easily enables co-medical staffs led by health nurses to use, give marks, and screen the persons for the purpose of performing health activities in respective districts finding out persons suspected of being dementia at an early stage, and adequately advising and guiding them. Also, this screening test can be used for the screening at the time of epidemiology investigation.
(3) N Type Mental Function Examination
The N type mental function examination is an old people""s mental function examination which aims to measure an intellectual function in wider range, by adding questions on concept formation, diagram duplication, space recognition, movement formation function, and the like to questions on memory, orientation, and calculation.
This test can be used for distinguishing whether aged change of the mental function is caused by normal aging or disordered dementia. However, this test mainly aims to be performed to the old people suspected of being demented. For this reason, the test is prepared so as to evaluate a dementia degree (level) at a wide range of 5 stages, that is, normal, boundary, slight dementia, moderate dementia, and severe dementia.
(4) Mental Status Questionnaire (MSQ)
This MSQ (Mental Status Questionnaire) has been developed for a large scale investigation of old people at homes in New York City in 1958. Since the investigation is for many people socially, physically, and mentally quite different from each other, the aim of the investigation is to be performed simply, objectively, and easily, and to provide a reliable index for a mental function disorder.
As for question items of the MSQ, most distinguishable ones have been selected from among the question items including an orientation, a memory, a calculation, general and personal information by a preparatory test for hundreds of people. One half of the question items are composed of those for testing the orientation, while the other half question items are composed of those for testing a general memory, so that the emphasis is laid on the orientation test.
(5) Mini-Mental State Examination (MMSE)
This MMSE has been developed in a short and standardized scale for a neurophysiological examination of inpatients as shown in FIG. 11.
Other various action observation scales (observation method) have been proposed as follows:
(6) Ezawa""s xe2x80x9cClinical Judgment Criteria of Senile Intelligencexe2x80x9d;
(7) Functional Assessment Staging Test (FAST);
(8) Clinical Dementia Rating (CDR);
(9) GBS Scale;
(10) N Mental State Scale For Old People (NM Scale).
Among above-mentioned prior art dementia judgment methods, it is found that the MMSE is a method securing a fixed reliability since the smaller the MMSE score on the abscissa in FIG. 1 becomes, the neuronal loss ratio N obtained from autopsy becomes larger, so that the mutual relationship is assured. However, since this method adopts a test form in which doctors always examine subjects (patients) in interviews, there have been problems as follows:
{circle around (1)} Since a questioner exists, the answer greatly depends on the special human relationship between the questioner and the subject, and is not always objectively and accurately obtained, resulting in variation of the judgment result.
{circle around (2)} While the subject is repeating the test, he or she may learn the examination contents, so that the objective judgment result can not be obtained.
{circle around (3)} The subject occasionally refuses to answer.
Thus, in the prior art diagnosis methods, an objective method for distinguishing an early-stage demented patient from a normal person has not been proposed. Furthermore, in order to use it for dementia screening, the diagnosis method must be performed in a short time, at a low cost, and treated easily. However, a practicable method which enables the diagnosis of the demented patient at an early stage has not yet been proposed by the prior art methods including the above-mentioned methods.
Also, the methods utilizing the above-mentioned SPECT, PET, and the like need extremely short-life radioisotope materials, a cyclotron is required as a part of this system, which results in a greatly high cost.
It is accordingly an object of the present invention to provide inexpensive method and apparatus for estimating the degree of neuronal impairment in the brain cortex, which enable an objective judgment of an early dementia disorder without men""s intervention for the judgment.
It has been widely known that human thinking, recognition, recall of memory, pleasantness/unpleasantness, mental fatigue, stress, and the like depend on an electrical action of a number of neurons in the brain.
Namely, it has been thought that signal transmission in a brain is performed by transmission of active potential impulses on nerve axons, and that the contents of the signal are encoded to a frequency of the impulses. When the action potential impulse reaches an excitatory synapse, electric current flows out of the connected neuron, through tissues outside the neurons, and returns to the original cell body. Since the current flow closely resembles that of a single current dipole, the electrical action of an individual neuron can be replaced with a single equivalent current dipole.
If activated neurons concentrate on a relatively limited place, their electric activity can be approximated by one or more such equivalent current dipoles.
In order to find out such current dipoles, the potentials (or magnetic field strengths) which appear at the positions of EEG (MEG) sensors on a scalp at the time when one or more current dipoles having an arbitrary moment are arbitrarily placed in the head are calculated, and the mean squared value of the errors between the calculated potentials and the potentials (or magnetic fields) measured by the sensors is calculated.
The current dipoles are moved until the position, the direction, and the value where the mean value of the squared errors becomes least are obtained, which is made an equivalent dipole.
If non-uniformity occurs in the neuronal activity in the cortex as a result of Alzheimer""s disease, this non-uniformity appears in the scalp potential. Since the scalp potential distribution is smooth, deviations from this smooth potential given as is mean square value reflect non-uniform neuronal activity in the cortex. This smoothness is numerically given by the mean dipolarity (approximate degree of equivalent dipole for measured potential) over a given period of time.
The present invention is based on well-known technologies indicated in the Japanese Patent Publication No.3-42897, the Japanese Patent Application Laid-open No.3-99630, the Japanese Patent No.2540728, and the like.
In the present invention developed from those basic technologies, it has become clear that a moment of a stochastic process, which is a statistic on time variation of the dipolarity, or the mean dipolarity on an alpha wave has a threshold value by which normal can be distinguished from dementia. Accordingly, it becomes possible to quantify dementia, in particular, Alzheimer""s disease, and to distinguish normal from dementia at a certain sensitivity and specificity.
Furthermore, the mean dipolarity fluctuates in time. This reflects the instability (standard deviation) of the neuronal activity. The instability generally increases along with the progress of dementia. The standard deviation indicating the fluctuation of such a mean dipolarity also has a threshold value, in which if the standard deviation becomes larger than the threshold value, the subject can be estimated as Alzheimer""s disease.
The relationship between such a mean dipolarity xe2x80x9cdxe2x80x9d and a standard deviation SD is shown in a brain impairment diagram of FIG. 2. Threshold values of the mean dipolarity and standard deviation divide the diagram in four domains {circle around (1)}-{circle around (4)}. The second and fourth quadrants {circle around (2)}, {circle around (4)} indicate Alzheimer""s disease and normal, respectively.
FIGS. 3A and 3B show MRI cross-sections of the head, and show the dipolarity values obtained by a computer simulation, where neurons in white zones are activated. FIG. 3A shows a normal example, in which neuronal activity is uniform over the white zone and the mean dipolarity indicates a large value xe2x80x9c99.862xe2x80x9d although the activated neurons spread over such a large part. Also, FIG. 3B simulates Alzheimer""s brain where white zones are separated by inactive neurons, in which the mean dipolarity is as low as xe2x80x9c97.057xe2x80x9d.
Accordingly, by obtaining the above-mentioned mean dipolarity xe2x80x9cdxe2x80x9d for each equivalent dipole, the mean dipolarity xe2x80x9cdxe2x80x9d and the neuron loss rate N can be graphed as shown by the characteristic curves in FIG. 1. The curve N is estimated from autopsy results of Alzheimer""s patients and their clinical data before autopsy.
Also, it has been clarified by the above-mentioned SPECT that the mean dipolarity of the alpha component is highly correlated to cerebral blood flow rate in specified regions of the cortex as the temporal and the temporal-parietal lobes, which is specific to the early Alzheimer""s disease.
On the other hand, in case a brain wave such as an alpha wave is measured by using the brain sensor or the brain magnetic sensor, two equivalent dipoles can be adopted since it is thought that the source of the wave is distributed over both hemispheres of the brain. However, even though two equivalent dipoles are required in order to specify the position of the active neuron, a single equivalent dipole is enough to judge the dipolarity.
Therefore, the inventor of the present invention separately has analyzed, as shown in FIGS. 4-7 for example, the case where the head is supposed to be a spherical shape (see FIGS. 4 and 6) and the case where the head is made a real shape (see FIGS. 5 and 7), in two models of the case where a single equivalent dipole is supposed (see FIGS. 4 and 5) and the case where two equivalent dipoles are supposed (see FIGS. 6 and 7), whereby it has been found that the envelopes connecting the peak values of the dipolarity values of the alpha component in the respective cases are consistent with each other.
Namely, in case of a single equivalent dipole, the location of the equivalent dipole vector is near a midline of the head which is different from the case of two equivalent dipoles. However, it has been found that the peak values of the mean dipolarities xe2x80x9cdxe2x80x9d do not have mutually much difference, and that whether the peak values are obtained for the real shape or the spherical shape does not make much difference.
A method for estimating degree of neuronal impairment in brain cortex is characterized in that a scalp potential of a subject is detected by mounting a plurality of EEG sensors on the scalp of a subject, the scalp potential is converted into numerical data to obtain a dipolarity, a statistic on a time variation of the dipolarity is obtained as dementia degree parameters of the subject, and the parameters are outputted.
Furthermore, in the method for estimating degree of neuronal impairment in brain cortex according to the present invention, the scalp potential may be detected by a terminal equipment, the data of the scalp potential may be sent to an operation center through a communication line, and the parameters required for a dementia estimation may be determined at the operation center to be sent back through the communication line to the terminal equipment for outputting.
An apparatus for preparing the neuronal impairment diagram according to the present invention may comprise a plurality of EEG sensors mounted on a scalp of a subject, a computing unit for converting an output signal of the EEG sensors into numerical data to obtain a dipolarity and for obtaining statistic on a time variation of the dipolarity as dementia degree parameters of the subject, and an output unit for outputting the parameters.
Furthermore, in the apparatus for estimating degree of neuronal impairment in brain cortex according to the present invention, the EEG sensor and the output unit may be provided in a terminal equipment, the computing unit may be provided in an operation center, and the terminal equipment and the operation center may be connected through a communication line.
The present invention may provide a program to be executed by a computer. For automatically judging a brain action, the program is provided with the steps of determining a dipolarity based on numerical data of a scalp potential of a subject detected by mounting a plurality of EEG sensors or MEG sensors on a scalp of the subject, judging a statistic on a time variation of the dipolarity as dementia degree parameters of the subject, and outputting the parameters.
Also, the present invention may provide a computer readable recording medium characterized in that the above-mentioned program is recorded.
Various modes may be applied to the above-mentioned method, apparatus therefor, program therefor, and recording medium therefor, as follows:
The above-mentioned dipolarity may comprise a value indicating an approximate degree, after a predetermined frequency component within the data is extracted, and based on the predetermined frequency component, at a time when one or more equivalent dipoles are determined in which a mean value of a squared error between a potential distribution which one or more current dipoles, supposed in the head, form at positions of the sensors and a measured potential of the sensors indicated by the data becomes minimized.
A spherical head model may be applied to the head in this case.
As the statistic, a moment of a stochastic process or a mean dipolarity indicating a mean value of a fixed number of peak values at a time when a plurality of dipolarities are obtained by sampling may be used. Alternatively, since a standard deviation increases as the mean dipolarity decreases with a high degree of correlation, the standard deviation indicating the fluctuation can be used instead of the mean dipolarity to obtain the same result.
The mean dipolarity or the standard deviation may be obtained by using a signal within a predetermined frequency component, not only the alpha component.
The data may be obtained by using an MEG sensor instead of the EEG sensor, and a magnetic field instead of the potential.
Also, whether the subject is normal or demented may be judged by comparing the mean dipolarity value with a predetermined threshold value, by comparing the standard deviation with a predetermined threshold value, or by a mutual relationship between the mean dipolarity and the standard deviation.
In addition, a kind and a degree of dementia may be judged by a relationship between the mean dipolarity and the standard deviation.
The dipolarity values can be derived based on a plural number of equivalent dipoles with a more complex head model although calculation becomes more complex.
The present invention is superior to other existing diagnosis tools as MMSE, SPECT, etc. in high reliability, high sensitivity, easy operation, non-invasiveness, short required time, and low cost.